First Constraint-Based Metabolic Model for an Archaea to be Published in Nature Reviews Molecular Systems Biology

Scientists from Pacific Northwest National Laboratory (PNNL) and the University of California-San Diego (UCSD) have completed the most advanced genome-scale metabolic model for a microbe in the domain Archaea, one of the three domains of life on Earth. This is also the first flux-balance analysis (FBA) ever applied to methanogenesis or Archaeal microorganisms. Their simulations accurately predicted cellular phenotypes under various conditions to better understand the biochemistry of energy conservation. The results will appear in Nature Reviews Molecular Systems Biology. Download PDF of this article.

The starting point was the 5-million base pair M. barkeri genome. Using a variety of biological information sources (see figure), the genome sequence was converted into an interlinked series of mathematical equations describing the detailed functioning of the cell. The resulting metabolic network model was then used by applying a constraint-based approach, or FBA. This approach uses linear optimization of all the equations to determine the steady-state flux of compounds and energy throughout the network under a given set of environmental conditions.

Simulation of cellular metabolism by this method generates predictions that can be used to design and carry out experiments. Where prediction and experiment agree, that aspect of the model is validated. Where prediction and experiment disagree, the model shows where additional information is needed and where the model may need improvement. Constraint-based methods can also incorporate physico-chemical, spatial, environmental, or gene regulatory information.

Methanogens are an attractive model system for these simulations because of their environmental and economic importance. In many anaerobic environments they carry out the final steps in degrading industrial, agricultural and toxic wastes. The resulting product, methane, contributes to the greenhouse effect when released to the atmosphere. On the positive side, methane is an important source of renewable or "green" energy and can be used to generate electricity or heat.

PNNL microbiologists Hans Scholten and Fred Brockman co-authored the paper with Adam Feist, Bernhard Palsson, and Trey Ideker, UCSD. The work was sponsored by PNNL's Biomolecular Systems Initiative and the National Institutes of Health. Sequence data were produced at the U.S. Department of Energy Joint Genome Institute.